COVALENT INTERACTIONS OF ESTROGENS IN TARGET TISSUES

了解雌二醇代谢在卵巢癌生物学中的作用 荷尔蒙了解其不同种类的生物学效应是至关重要的。 代谢产物。这个项目与蜂窝网络有关 16α-羟雌酮和2-羟雌酮的相互作用 雌二醇代谢物的生物学特性不同于 母体荷尔蒙。与16α-羟雌酮形成共价键 通过席夫碱和随后的Heyns形成的伯氨基 重新编排。2-羟雌酮与亲核试剂如 巯基也与生物分子形成共价键。 这两个过程都被证明是在体外对细胞成分进行的 和在体内，被认为是重要的生理学和 雌激素作用的病理生理学。将在以下网站上寻求准确的信息 雌激素靶标中这种共价键形成的亚细胞位置 组织和特定生物大分子的性质 参与了这些互动。这些生物的生物学后果 将在体外和体内研究中探索这一过程， 合适的实验模型。预计这些研究将 阐明这些天然雌激素在荷尔蒙相关的 疾病。

To understand the role of metabolism of estradiol in the biology of the hormone it is essential to know the biological effects of its diverse metabolic products. This project is concerned with the cellular interactions of 16Alpha-hydroxyestrone and 2-hydroxyestrone, major metabolites of estradiol with biological properties distinct from those of the parent hormone. 16Alpha-hydroxyestrone forms covalent linkages with primary amino groups via Schiff base formation and subsequent Heyns rearrangement. 2-Hydroxyestrone reacts avidly with nucleophiles such as sulfhydryl groups to also form covalent bonds with biological molecules. Both processes have been shown to proceed with cellular components in vitro and in vivo and are considered to be of importance in the physiology and pathophysiology of estrogen action. Precise information will be sought on the subcellular sites of such covalent bond formation in estrogen target tissues and on the nature of the specific biological macromolecules involved in these interactions. The biological consequence of these processes will be explored in in vitro and in vivo studies employing appropriate experimental models. It is expected that these studies will shed light on the role of these natural estrogens in hormonally linked diseases.